Ephedrine salts and oil solutions thereof



Patented June 7, 1932 UNITED STATES PATENT OFFICE EDMOND E. MOORE AND EDGAR B. CARTER, OF INDIANAPOLIS, INDIANA, ASSIGNOBS, BY MESNE ASSIGNMENTS, TO ABBOTT LABORATORIES, OF CHICAGO, ILLINOIS, A

CORPORATION OF ILLINOIS EPHEDRINE SALTS AND OIL SOLUTIONS THEREOF Ho Drawing.

It is the purpose of our invention to produce an ephedrine salt, and it is a further object of our invention to produce an ephedrine salt which shall be soluble in oil, preferably mineral oil (liquid petrolatum).

Ephedrine has been found of decided benefit in the treatment of certain respiratory affections as of the nose, throat and associated organs. \Vhen used in such treatment there is an initial stin which creates an unpleasant sensation and renders the use of the same objectionable to some patients.

We have discovered that this sting is due to the fact that the ephedrine is a strongly basic alkaloid.

We have discovered that when the alkaloid ephedrine is combined with a fatty acid it produces a salt which, when used, does not cause the stinging sensation produced by the alkaline nature of the alkaloid ephedrine, and this salt is soluble in mineral oil. While we have specifically stated that one of the objects is to provide an ephedrine derivative which is soluble in mineral oil it will be understood that the product is also soluble in other oils and in fats, and furthermore it will be understood that while we produce a salt, which is particularly useful because of its solubility in oil and because of its nonstinging nature such salt has other uses and other applications. One method of producing a salt of this character is by combining ephedrine with a fatty acid having not less than nine carbon atoms. The method of preparation may consist of intimately mixin in molecular proportions the ephedrine and preferably an unsaturated fatty acid having preferably not less than nine carbon atoms. In those cases where the fatty acid is solid at room temperature it is melted before the ephedrine is stirred in.

The resultant compound is also soluble in water giving a soapy solution or a collodial suspension. The ephedrine salts or soaps above produced greatly lower the surface tension so that the resultant solution tends to form foam and bubbles when agitated. These salts are quite useful as emulsifying agents The ephedrine salts thus produced, that is the ephedrine salts produced by the com- Applicatlon filed March 28, 1930. Serial No. 440,152.

hinin of ephedrine with a fatty acid of not less t an nine carbon atoms is soluble in mineral oil (liquid petrolatum) and the solubility of these salts in mineral oil increases with the number of carbon atoms in the acid from which the ephedrine salt is made, even though the solution of the salts formed with the fatty acids having the higher carbon content becomes solid at room temperatures.

Various fatty acids may be used and combined with the ephedrineto produce the ephedrine salts and any of the resultant salts may be combined or mixed with mineral or other oils or fats and will be heldin solution therein, although so far as we have been able to determine at resent we have found that combining ephe rine with oleic acid or with erucic acid produces an ephedrine salt which is more readily soluble in mineral oil.

However, the following are formulas of ephedrine salts which are quite satisfactory.

muses (on CHCHa cnmmoocwnn cm.

comcmomcacm ona moocwnnwom.

qmcammcncn,

CHIN I )HCHI.

canomomcncm ca nnflooownnnc a- Cs acH(0 )CHCHa CH;NH OOC(CHalxeCHacnncrnon)once cmnmoocwnghcmc mcmomcncm cammoocwamcm.

omscmomcncna CHaNHgOGC CH2) u a mmcmomcncn CHaNHgOOC(CH2l1s H- (amen omcncna CH N H OOC (C a)1sC a- CGH5CH(OH)CHCH:|

on, n,ooo(cnfl).ion=en,.

canon 01; cHcH,

CH NHgOOC (CH2)1 CHCH.CH( OH) (C :)s a- The compounds formed by the union of ephedrine with unsaturated fatt acids are more soluble in mineral oil, such or instance as light liquid petrolatum and have less tendency to form solid solution, although we have found that even the compounds formed by the union of ephedrine with saturated fatty acid Where the fatty acids have not less than nine carbon atoms are quite soluble in oil and fats.

We have also found that one molecular equivalent of ephedrine combines with exactly one molecular equivalent of fatty acid.

We claim the following:

1. An ephedrine salt consisting of ephedrine combined with a fatty acid having more than eight carbon atoms.

2. An ephedrine salt consisting of ephedrine combined with an unsaturated fatty acid having more than eight carbon atoms.

3. An ephedrine salt consisting of ephedrine combined with erucic acid.

4. An ephedrine salt consisting of cpl drine combined with erucic acid.

5. An ephedrine salt consisting of eph drine combined with ricinoleic acid.

In witness whereof, we have hereunto set our hands at Indianapolis, Indiana, this 27th day of March, A. I). one thousand nine hundred and thirty.

EDMOND E. MOORE. EDGAR B. CARTER.

CERTIFICATE OF CORRECTION.

Patent No. 1,861,543. June 7, 1932.

EDMOND E. MOORE, ET AL.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows: Page 2, line 24, claim 4, for "erucic" read oleic; and that the said Letters Patent should be read with this correction therein that the same may onform to the record of the case in the Patent Office.

Signed and sealed this 30th day of January, A. D. 1934.

F. M. Hopkins (Seal) Acting Commissioner of Patents.

The compounds formed by the union of ephedrine with unsaturated fatt acids are more soluble in mineral oil, such or instance as light liquid petrolatum and have less tendency to form solid solution, although we have found that even the compounds formed by the union of ephedrine with saturated fatty acid Where the fatty acids have not less than nine carbon atoms are quite soluble in oil and fats.

We have also found that one molecular equivalent of ephedrine combines with exactly one molecular equivalent of fatty acid.

We claim the following:

1. An ephedrine salt consisting of ephedrine combined with a fatty acid having more than eight carbon atoms.

2. An ephedrine salt consisting of ephedrine combined with an unsaturated fatty acid having more than eight carbon atoms.

3. An ephedrine salt consisting of ephedrine combined with erucic acid.

4. An ephedrine salt consisting of cpl drine combined with erucic acid.

5. An ephedrine salt consisting of eph drine combined with ricinoleic acid.

In witness whereof, we have hereunto set our hands at Indianapolis, Indiana, this 27th day of March, A. I). one thousand nine hundred and thirty.

EDMOND E. MOORE. EDGAR B. CARTER.

CERTIFICATE OF CORRECTION.

Patent No. 1,861,543. June 7, 1932.

EDMOND E. MOORE, ET AL.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows: Page 2, line 24, claim 4, for "erucic" read oleic; and that the said Letters Patent should be read with this correction therein that the same may onform to the record of the case in the Patent Office.

Signed and sealed this 30th day of January, A. D. 1934.

F. M. Hopkins (Seal) Acting Commissioner of Patents. 

